EFFECTS OF LIDOCAINE ON CYTOSOLIC PH REGULATION AND STIMULUS-INDUCED EFFECTOR FUNCTIONS IN ALVEOLAR MACROPHAGES

Local anesthetics influence a variety of stimulus-induced effector fun ctions in leukocytes. The present study determined the effects of lido caine on intracellular pH (pH(i)) regulation, superoxide production, a nd tumor necrosis factor-alpha (TNF-alpha) release in alveolar macroph ages (m phi). Resident m phi were obtained by bronchoalveolar ravage o f rabbits. The cells were subjected to an intracellular acid load, and subsequent pH(i) recovery was followed in the presence or absence of bafilomycin A(1), a specific inhibitor of V-type H+-translocating ATPa se (V-ATPase) or amiloride, an inhibitor of Na+/H+ exchange. Lidocaine slowed pH(i) recovery in a dose-dependent manner. Pretreatment (1 h) with 2.5 mM lidocaine abolished Na+/H+ exchange and reduced the V-ATPa se-mediated component of pH(i) recovery. Lidocaine also significantly depressed the superoxide production induced by phorbol ester. TNF-alph a release induced by endotoxin was not affected significantly by the l ocal anesthetic. Macrophage viability (trypan blue exclusion) and cell ular ATP concentration were unaffected. These results indicate that li docaine inhibits pH(i) regulatory mechanisms in alveolar m phi. This d isruption of pH(i) regulation could contribute to inhibitory actions o f lidocaine on m phi effector functions.